Pathway: tRNA processing in the mitochondrion
Reactions in pathway: tRNA processing in the mitochondrion :
tRNA processing in the mitochondrion
Each strand of the circular mitochondrial genome is transcribed to yield long polycistronic transcripts, the heavy strand transcript and the light strand transcript, which are then cleaved to yield tRNAs, rRNAs, and mRNAs (Mercer et al. 2011, reviewed in Suzuki et al. 2011, Rossmanith 2012, Powell et al. 2015). Mitochondrial RNase P, which is completely distinct from nuclear RNase P in having different protein subunits and no RNA component, cleaves at the 5' ends of tRNAs. RNase Z, an isoform of ELAC2 in mitochondria, cleaves at the 3' ends of tRNAs. (A different isoform of ELAC2 serves as RNase Z in the nucleus.) Unknown nucleases make additional cleavages near the 5' end of MT-CO3, the 5' end of CO1, the 5' end of CYB, and the 3' end of ND6. TRNT1 (CCA-adding enzyme) then post-transcriptionally polymerizes the universal acceptor sequence CCA onto the 3' ends of the cleaved tRNAs. In yeast, plants, and protozoa additional tRNAs encoded in the nucleus are imported into mitochondria from the cytosol (reviewed in Schneider 2011), however human mitochondria encode a complete complement of 22 tRNAs required for translation and tRNA import has not been observed in mammals. Mutations that affect mitochondrial tRNA processing cause human diseases that are generally characterized by abnormalities in energy-requiring tissues such as brain and muscle (reviewed in Suzuki et al. 2011, Sarin and Leidel 2014).
Genes encoding transfer RNAs (tRNAs) are transcribed by RNA polymerase III in the nucleus and by mitochondrial RNA polymerase in the mitochondrion.
In the nucleus transcription reactions produce precursor tRNAs (pre-tRNAs) that have extra 5' leaders, 3' trailers, and, in some cases, introns which are removed by enzymes and enzyme complexes: RNase P cleaves the 5' leader, RNase Z cleaves the 3' trailer, TRNT1 polymerizes CCA onto the resulting 3' end, the TSEN complex cleaves at each end of the intron, and the tRNA ligase complex ligates the resulting exons (reviewed in Rossmanith et al. 1995, Phizicky and Hopper 2010, Suzuki et al. 2011, Abbott et al. 2014, Li and Mason 2014). The nucleotides within tRNAs undergo further chemical modifications such as methylation and deamination by a diverse set of enzymes (reviewed in Helm and Alfonzo 2014, Boschi-Muller and Motorin 2013). The order of events for each tRNA is not fully known and the understanding of the overall process is complicated by the retrograde (cytosol to nucleus) transport of tRNAs.
In the mitochondrial matrix transcription produces long precursor RNAs, H strand transcripts and an L strand transcript, that are cleaved by mitochondrial RNase P (an entirely proteinaceous complex), ELAC2, and other nucleases to yield 12S rRNA, 16S rRNA, mRNAs, and pre-tRNAs lacking 3' CCA sequences (reviewed in Van Haute et al. 2015). TRNT1 polymerizes an untemplated CCA sequence onto the 3' ends of the pre-tRNAs and chemical modifications are made to several nucleotides in the tRNAs.
In the nucleus transcription reactions produce precursor tRNAs (pre-tRNAs) that have extra 5' leaders, 3' trailers, and, in some cases, introns which are removed by enzymes and enzyme complexes: RNase P cleaves the 5' leader, RNase Z cleaves the 3' trailer, TRNT1 polymerizes CCA onto the resulting 3' end, the TSEN complex cleaves at each end of the intron, and the tRNA ligase complex ligates the resulting exons (reviewed in Rossmanith et al. 1995, Phizicky and Hopper 2010, Suzuki et al. 2011, Abbott et al. 2014, Li and Mason 2014). The nucleotides within tRNAs undergo further chemical modifications such as methylation and deamination by a diverse set of enzymes (reviewed in Helm and Alfonzo 2014, Boschi-Muller and Motorin 2013). The order of events for each tRNA is not fully known and the understanding of the overall process is complicated by the retrograde (cytosol to nucleus) transport of tRNAs.
In the mitochondrial matrix transcription produces long precursor RNAs, H strand transcripts and an L strand transcript, that are cleaved by mitochondrial RNase P (an entirely proteinaceous complex), ELAC2, and other nucleases to yield 12S rRNA, 16S rRNA, mRNAs, and pre-tRNAs lacking 3' CCA sequences (reviewed in Van Haute et al. 2015). TRNT1 polymerizes an untemplated CCA sequence onto the 3' ends of the pre-tRNAs and chemical modifications are made to several nucleotides in the tRNAs.
This superpathway encompasses the processes by which RNA transcription products are further modified covalently and non-covalently to yield their mature forms, and the regulation of these processes. Annotated pathways include ones for capping, splicing, and 3'-cleavage and polyadenylation to yield mature mRNA molecules that are exported from the nucleus (Hocine et al. 2010). mRNA editing and nonsense-mediated decay are also annotated. Processes leading to mRNA breakdown are described: deadenylation-dependent mRNA decay, microRNA-mediated RNA cleavage, and regulation of mRNA stability by proteins that bind AU-rich elements.psnRNP assembly is also annotated here.
The aminoacylation of mature tRNAs is annotated in the "Metabolism of proteins" superpathway, as a part of "Translation".